The present invention relates to a method of treating inflammatory bowel disease comprising administering a pharmaceutical composition comprising a 6-aminopyridin-3-ol compound or a pharmaceutically acceptable salt thereof as an active ingredient to a subject.
Angiogenesis is the process through which new capillary vessels form from existing micro vessels. Angiogenesis normally occurs during embryonic development, tissue regeneration, wound healing, and corpus luteum development that is a cyclic change of female reproductive system, and even in these cases, angiogenesis occurs under stringent control.
For adults, endothelial cells very slowly grow, and compared to other kinds of cells, they do not divide well. Angiogenesis occurs such that in general, due to the stimulus of a promotion factor for angiogenesis, vascular basal membrane decomposes by protease, and endothelial cells move, proliferate, and differentiate, leading to formation of lumen and reconstruction of vessels, forming new capillary vessels.
However, in some cases, angiogenesis may not be autonomously controlled but pathologically grows to cause disease. Examples of angiogenesis-associated disease that occurs in a pathologic state are hemangioma, angiofibroma, vascular malformation, and cardiovascular disease, such as arteriosclerosis, vascular adhesion, or scleroedema, and examples of angiogenesis-associated ophthalmic disease are keratoplasty angiogenesis, angiogenic glaucoma, diabetic retinopathy, neovascular corneal disease, macular degeneration, pterygium, retinal degeneration, retrolental fibroplasia, and trachoma. Chronic inflammatory disease, such as arthritis, dermatology disease, such as acne, psoriasis, capillarectasia, granuloma pyogenicum, or dermatitis seborrheica, Alzheimer's disease, and obesity are also associated with angiogenesis, and the growth and metastasis of cancer are necessarily dependent on angiogenesis.
In particular, in the case of cancer, angiogenesis plays a critical role in the growth and metastasis of cancer cells. Tumors are fed with nutrition and oxygen required for the growth and proliferation through new blood vessels, and new blood vessels permeated into tumor allow metastasizing cancer cells to enter a blood circulation system, causing metastasis of cancer cells. The major death cause of cancer patients is metastasis, which often leads to the failure of clinical chemotherapy or immuno-therapy performed to increase survival rate of cancer patients.
Arthritis, which is a representative inflammatory disease, is caused by abnormal autoimmune system. However, when the disease progresses, chronic inflammation developed in synovial cavity between joints induces angiogenesis and destroys cartilage. That is, cytokines inducing inflammation help proliferation of synovial cells and vascular endothelial cells in synovial cavity, and while angiogenesis progresses, joint pannus, which is a connective tissue occurring in a cartilage site, is formed to destroy cartilage acting as a cushion.
Each year, many ophthalmic diseases cause blindness in hundreds of people worldwide, and induce angiogenesis. Representative examples of such diseases are macular degeneration, which occurs in old people, diabetic retinopathy, premature infant retinopathy, neovascular glaucoma, and corneal disease caused by neovascularization cause angiogenesis. From among these disease, diabetic retinopathy is a complication of diabetes that causes blindness by invasiveness of retinal capillary vessels into hyaloid.
Psoriasis characterized with red spots and scaly skin is also a chronic proliferative disease that develops in the skin. Psoriasis is not treatable and accompanies pains and malformation. In a normal case, horny cells proliferate once a month. However, in the case of psoriasis patients, horny cells proliferate at least once a week. This rapid proliferation needs much blood, which is why angiogenesis actively occurs.
Angiogenesis inhibitors can be used as a therapeutic agent for these angiogenesis-associated diseases. Accordingly, research into how to treat these diseases by inhibiting angiogenesis is actively being performed. In general, angiogenesis inhibitors are administered to patients for a long period of time, so that they desirably need to be non-toxic and orally administrable. Accordingly, there is a need to develop as an angiogenesis inhibitor a drug whose toxicity is negligible.